POS0473 ASSESSMENT OF THE LEVELS OF 14-3-3Η PROTEIN, A NOVEL BIOMARKER, IN PATIENTS WITH RHEUMATOID ARTHRITIS AND ITS CORRELATION WITH DISEASE ACTIVITY
Authors: R. Chawla, P. Jain
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid Arthritis (RA) is a common inflammatory arthritis. Current ACR-EULAR classification criteria for RA include joint involvement, immunological markers {Rheumatoid factor (RF) and Anti-citrullinated protein antibody (ACPA)}, inflammatory markers {Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)}, and symptom duration. But these markers are not 100% accurate for RA. A meta-analysis found sensitivity and specificity of RF and ACPA to be 69% &amp; 85% and 67% &amp; 95% respectively <sup>[1]</sup>. There is a need for new biomarkers that can increase accuracy of RA diagnosis, one such marker is 14-3-3η protein which is a pro-inflammatory mediator and can serve as a diagnostic and prognostic marker and a potential therapeutic target in RA patients <sup>[2,3]</sup>. <h3>Objectives:</h3> Assess 14-3-3η protein levels in RA patients. Compare positivity rates of 14-3-3η to RF and ACPA. See association between 14-3-3η levels and disease activity. <h3>Methods</h3> 78 RA cases and 78 age &amp; sex matched healthy controls were enrolled. Inclusion criteria were RA diagnosis (as per 2010 ACR/EULAR criteria), age above 18 years. Patients with any other disease &amp; pregnant females were excluded. DAS28-ESR scoring was done. Blood was collected and tested for ESR, CRP, RF, ACPA, and 14-3-3η protein using ELISA. <h3>Results</h3> Mean age in years in cases and controls was 41.71 and 41.37 respectively. 88% participants were females. Median disease duration was 32.5 months, median tender joint count was 4.50 and median swollen joint count was 1. Mean ESR in cases &amp; controls was 32.41 ± 18.8 mm and 10.79 ± 3.49 mm respectively (p=0.001). CRP was positive in 70.5% cases &amp; 11.5% controls (p &lt; 0.001), RF in 88.5% cases &amp; 11.5% controls (p &lt; 0.001) and ACPA in 73% cases &amp; none of the controls (p &lt; 0.001). Mean 14-3-3η protein levels (ng/ml) were 7.61 ± 2.55 in cases and 0.73 ± 0.43 in controls (p &lt; 0.001); 7.64 ± 2.62 in seropositive cases and 7.18 ± 1.62 in seronegative cases (p =0.673). There was a significant difference between 14-3-3η protein levels in seronegative patients and controls (p= 0.001).14-3-3η protein levels had no correlation with RF/ACPA positivity (p= 0.965) (Figure 1). Mean 14-3-3η protein levels (ng/ml) in patients in "remission" (as per DAS28-ESR) was 5.71± 2.50, while the levels(ng/ml) in patients in low, moderate, and high disease activity were 8.58 ± 4.04, 6.98 ± 1.00 and 8.36 ± 2.62 respectively (p= 0.020). The sensitivity and specificity of RF were 88.5% each, of 14-3-3η was 100% and 90.1% respectively and that of ACPA were 73.1% and 100% respectively. 14-3-3η protein had higher sensitivity than the other 2 biomarkers (p=0.001). ROC curve suggested the ideal cut-off of 14-3-3η protein to be 1.14 ng/ml with a sensitivity of 100% and a specificity of 90.1%. When RF and ACPA were combined, the sensitivity and specificity were 96.9% and 88.5% respectively. When 14-3-3η was combined with RF, sensitivity, and specificity was 100% and 79.7% respectively while it was 100% and 90.1% respectively when 14-3-3η was combined with ACPA. Thus, 14-3-3η protein increased the sensitivity of RF and ACPA. <h3>Conclusion</h3> 14-3-3η protein levels are significantly raised in both seropositive and seronegative RA patients and it does not depend on RF or ACPA. 14-3-3η protein increases the sensitivity of RF and ACPA in RA diagnosis and should be included as an additional test in evaluation of RA patients. <h3>References</h3> [1]Nishimura K, Sugiyama D, Kogata Y, Tsuji G, Nakazawa T, Kawano S et al. Meta-analysis: Diagnostic Accuracy of Anti–Cyclic Citrullinated Peptide Antibody and Rheumatoid Factor for Rheumatoid Arthritis. Ann Intern Med. 2007;146(11):797-808. [2]Kilani RT, Maksymowych WP, Aitken A, Boire G, St-Pierre Y, Li Y et al. Detection of high levels of 2 specific isoforms of 14-3-3 proteins in synovial fluid from patients with joint inflammation. J Rheumatol. 2007;34(8):1650-1657. [3]Maksymowych WP, van der Heijde D, Allaart CF, Landewé R, Boire G, Tak PP et al. 14-3-3η is a novel mediator associated with the pathogenesis of rheumatoid arthritis and joint damage. Arthritis Res Ther. 2014;16(2):R99. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.